CN110998296A - Analysis testing device - Google Patents

Abstract

An analytical test device (12) comprising: one or more light emitters (13) configured to emit a first wavelength range (Δ λ)_a) The light inside. The analytical test device (12) further comprises one or more first light detectors (14), each first light detector (14) being sensitive to a second wavelength range (Δ λ) around the first wavelength_b) And (4) sensitivity. The analytical test device (12) further comprises one or more second light detectors (15), each second light detector (15) being responsive to a third wavelength range (Δ λ) around the second wavelength_c) Sensitive, the second wavelength being different from the first wavelength. The analytical test device (12) further comprises a calibration module (16) configured to receive signals (19,20) from the first and second light detectors (14,15) and to base them on the signals from the light sourcesThe difference in weight of the signals (19,20) of the first and second light detectors (14,15) produces a correction signal (21). The analytical test device (12) is configured such that light from the light emitter (13) reaches the first and second light detectors (14,15) via a light path comprising the sample receiving portion (7).

Description

Analysis testing device

Technical Field

The present invention relates to an analytical test device.

Background

Biological tests for the presence and/or concentration of analytes may be conducted for a variety of reasons, including, among other applications, preliminary diagnosis, screening for the presence of controlled substances, and management of long-term health conditions.

Lateral flow devices (also known as "lateral flow immunoassays") are one type of biological test. Lateral flow devices can be used to test a liquid sample (e.g., saliva, blood, or urine) for the presence of an analyte. Examples of lateral flow devices include home pregnancy tests, home ovulation tests, tests for other hormones, tests for specific pathogens, and tests for specific drugs. For example, EP 0291194 a1 describes a lateral flow device for performing pregnancy tests.

In a typical lateral flow test strip, a liquid sample is introduced at one end of the porous strip and then drawn along the porous strip by capillary action (or "wicking"). A portion of the lateral flow strip is pretreated with label particles that are activated by a reagent that binds to the analyte to form a complex if the analyte is present in the sample. The bound complex and unreacted labeled particles continue to propagate along the lateral flow strip before reaching the test zone pretreated with the immobilized binding reagent that captures the bound complex of analyte and labeled particles, but not the unreacted labeled particles. The marker particles have a distinct color or other detectable optical or non-optical characteristic, and the development of the concentration of the marker particles in the test area provides an observable indication of the detected analyte. Lateral flow test strips may be based on colorimetric labeling using, for example, gold or latex nanoparticles, fluorescent labeling molecules, or magnetic labeling particles.

Another biological test comprises an assay (assay) performed in a liquid contained in a container (e.g. a vial, a PCR well/plate, a cuvette or a microfluidic cell). Liquid assays can be based on colorimetric or fluorometric measurements. An advantage of some liquid-based assays is that they allow for testing using extremely small (e.g., picoliter) volumes.

Sometimes, it is only necessary to determine the presence or absence of an analyte, i.e. a qualitative test. In other applications, an accurate concentration of the analyte, i.e. a quantitative test, may be required. For example, WO 2008/101732 a1 describes an optical measuring instrument and measuring device. The optical measurement instrument includes: at least one source for providing at least one electromagnetic beam to irradiate the sample and interact with a specimen within the sample, at least one sensor for detecting an output of the interaction between the specimen and the electromagnetic beam, an integrally formed mechanical stage for optical and electronic components, and a sample holder for holding the sample. The at least one source, the at least one sensor and the mechanical stage are integrated in one monolithic optoelectronic module, and the sample holder is connectable to the module.

Summary of The Invention

According to a first aspect of the present invention, there is provided an analytical test device comprising one or more light emitters configured to emit light in a first wavelength range. The analytical test device also includes one or more first photodetectors, each sensitive to a second wavelength range around the first wavelength. The analytical test device also includes one or more second light detectors, each second light detector being sensitive to a third range of wavelengths around a second wavelength, the second wavelength being different from the first wavelength. The analytical test device also includes a correction module configured to receive signals from the first photodetector and the second photodetector and to generate a correction signal based on a difference in weight of the signals from the first photodetector and the second photodetector. The analytical test device is configured such that light from the light emitter reaches the first light detector and the second light detector via an optical path that includes the sample receiving portion.

The analytical test device may be configured such that, in response to a sample placed in the sample receiving portion, the first and second light detectors receive substantially equal amounts of light scattered from each portion of the sample within the sample receiving portion. The second and third ranges may not overlap or do not significantly overlap. The optical path may not include any beam splitter. The optical path may not include any lenses.

The plurality of first light detectors and the plurality of second light detectors may be arranged in an alternating manner.

A part of each first light detector or each first light detector may extend in the first direction, and a part of each second light detector or each second light detector may extend in the first direction. The first and second light detectors, or parts thereof, may be interleaved in a second direction substantially perpendicular to the first direction.

The plurality of first light detectors may be arranged in a first lattice and the plurality of second light detectors may be arranged in a second lattice. The first lattice and the second lattice may be arranged to intersect each other.

The light path may further comprise a light diffuser disposed between the sample receiving portion and the light detector.

The optical path may be configured such that the first and second photodetectors receive light transmitted through the sample receiving portion.

The optical path may be configured such that the first and second light detectors receive light reflected from the sample receiving portion.

Each first light detector may include a first photosensitive material sensitive to a second wavelength range, and each second light detector may include a second photosensitive material sensitive to a third wavelength range.

Each first photodetector may include a photosensitive material and a first filter. The first filter may be arranged to filter light arriving via the optical path, transmit the second wavelength range, and attenuate the third wavelength range. Each second photodetector may include a photosensitive material and a second filter. The second filter may be arranged to filter light arriving via the optical path, transmit the third wavelength range, and attenuate the second wavelength range.

Each first light detector may include a light-sensitive material and each second light detector may include a light-sensitive material. The analytical test device may also include a first filter corresponding to each first light detector. The first filter may be arranged to filter light arriving via the optical path, transmit the second wavelength range, and attenuate the third wavelength range. The analytical test device may also include a second filter corresponding to each second light detector. The second filter may be arranged to filter light arriving via the optical path, transmit the third wavelength range, and attenuate the second wavelength range.

Each first photodetector may include a photosensitive material and a first resonant cavity configured to have a resonant wavelength within a second wavelength range. Each second photodetector may include a photosensitive material and a second resonant cavity configured to have a resonant wavelength within a third wavelength range.

The photosensitive material may comprise two or more different materials. Two or more materials may be mixed, compounded, blended, and/or arranged in a layered structure. The photoactive material may be a blend of n-type and p-type organic semiconductors.

Each light emitter may be in the form of an organic light emitting diode.

The one or more organic light emitting diodes may be disposed on one or more glass substrates. The one or more organic light emitting diodes may be disposed on one or more plastic substrates.

The first photodetector and the second photodetector may be in the form of organic photodetectors. The first and second photodetectors may be in the form of inorganic photodetectors.

The first photodetector and the second photodetector may be in the form of top absorption organic photodetectors.

The first photodetector and the second photodetector may be in the form of bottom absorption organic photodetectors.

The correction signal may be generated according to the following equation:

wherein I_CTo correct the signal, I¹_nIs the signal from the nth one of the N first photodiodes, I²_nFor the signal from the nth of the N second photodiodes, α is a predetermined weighting factor, and N is a real positive integer satisfying N ≧ 1.

The correction module may include a microprocessor or microcontroller.

The correction module may include a summing amplifier circuit configured to generate a correction signal based on inputs received from the first and second photodetectors.

The first wavelength may be in a first wavelength range, the second wavelength may be in the first wavelength range, and the analytical test device may be configured to measure an absorbance (absorbance) of the sample.

The first wavelength can be outside of a first wavelength range, the second wavelength can be outside of the first wavelength range, and the analytical test device is configured to measure fluorescence of the sample.

The sample receiving portion of the optical path can be configured to receive a lateral flow test strip. The sample receiving portion of the optical path may be configured to receive a cuvette. The sample receiving portion of the optical path may be configured to receive a test well plate. The sample receiving portion of the optical path may be configured to receive all, a portion, or a channel of the microfluidic device.

The analytical test device may further comprise a sample mounting stage which is movable between a loading position and one or more measurement positions in which all or part of the mounted sample is disposed in the sample receiving portion of the optical path.

The analytical test device may further include a drive device configured to move the sample mount between the loading position and the one or more measurement positions.

The analytical test device may further include a liquid delivery path for delivering a liquid sample received proximate an end of the liquid delivery path through the sample receiving portion of the optical path.

The lateral flow test device may include an analytical test device and a lateral flow test strip arranged such that the test region is disposed within the sample receiving portion.

The lateral flow test strip may include a labeling particle. The absorption of the marking particles may be greater in the second wavelength range than in the third wavelength range.

According to a second aspect of the present invention, there is provided a method of analysing a sample using an analytical test device or a lateral flow test device. A method of analyzing a sample includes receiving signals from a first photodetector and a second photodetector. The method of analyzing a sample further includes generating a corrected signal based on a weighted difference of signals from the first photodetector and the second photodetector.

According to a third aspect of the present invention, there is provided a method of determining one or more weighting coefficients for use in determining a correction signal in a method of analysing a test device or analysing a sample. The method of determining one or more weight coefficients comprises: the light of one or more of the optical transmitters is modulated according to a known time-varying signal, and one or more of the weighting coefficients are iteratively adjusted so as to minimize or eliminate the time-varying signal in the correction signal.

Brief Description of Drawings

Certain embodiments of the invention will now be described, by way of example, with reference to figures 3 to 22 and 24 to 29 of the accompanying drawings, in which:

FIG. 1 illustrates an emission side differential analysis test device;

FIG. 2 shows normalized spatial intensity distributions of light emitters used in the transmit side differentiation analysis test shown in FIG. 1;

FIG. 3 shows a first receive-side differential analysis test apparatus;

FIG. 4 is a partial perspective view of a lateral flow test strip reader incorporating a first receiving-side differential analysis testing device;

FIG. 5 shows a lateral flow test strip;

FIG. 6 illustrates the fiber structure of a lateral flow test strip;

FIG. 7 shows an absorption spectrum of a marker particle used in a lateral flow test strip;

FIGS. 8-10 illustrate a process for correcting background non-uniformities of a lateral flow test strip;

fig. 11 is a cross-sectional view of a bottom absorption organic photodiode;

fig. 12 is a cross-sectional view of a top absorption organic photodiode;

FIG. 13 shows a second receive-side differential analysis test apparatus;

14A and 14B show plan views of a first exemplary layout of a light detector and filter for a second receive-side differentiation analysis testing device;

FIG. 15 illustrates emission and absorption characteristics corresponding to one example combination of a light emitter and a filter suitable for measuring marker particles in the form of gold nanoparticles;

FIG. 16A illustrates a plan view of a second exemplary layout of a light detector and filter for a second receive-side differencing analysis test device;

FIG. 16B illustrates a plan view of a third exemplary layout of a photodetector and filter for a second receive-side differencing analysis test device;

FIG. 17 is a cross-sectional view of an organic photodiode including an optically resonant microcavity;

fig. 18 shows external quantum efficiency spectra corresponding to the first, second, and third examples of the organic photodiode shown in fig. 17;

FIG. 19 is a circuit diagram of an amplified adder circuit;

FIG. 20 shows a receiving side differential analysis test device based on transmitted light;

FIG. 21 shows a receiving-side differentiation analysis test device based on reflected light;

FIG. 22 is a cross-sectional view of a lateral flow test device including a receiving side differential analysis test device;

FIG. 23 shows a test area of a lateral flow test strip housed in an emission side differential analytical test device;

fig. 24A to 24D compare the stability of organic light emitting diodes disposed on a glass substrate and a plastic substrate;

FIG. 25 illustrates a method of determining one or more weight coefficients for a receiving-side differential analysis test device;

FIG. 26 shows a fourth receive-side differential analysis testing device;

FIG. 27 shows a fifth receive-side differential analysis test apparatus;

fig. 28 shows a sixth reception-side differential analysis test apparatus; and

fig. 29 shows a seventh reception-side differentiation analysis test apparatus.

Detailed description of some embodiments

The size and cost of the detector can be reduced if the number and complexity of the optical elements in the quantitative detector can be reduced. This would be particularly advantageous for hand-held or portable test devices as well as disposable home test kits.

If the signal-to-noise ratio of the measurement can be improved, the minimum threshold for detecting the analyte will be improved. Furthermore, an improvement in signal-to-noise ratio may allow for determination of analyte concentrations with improved resolution.

Transmitting side differentiation analysis testing device

Fig. 1 shows a transmit side differentialanalysis test device 1, which is useful for understanding the present invention. The emission-side differentialanalysis testing device 1 includes afirst light emitter 2 and asecond light emitter 3 that emit light 4, 5 onto alight path 6 that includes a sample-receivingportion 7. Alight detector 8 or several identicallight detectors 8 are arranged at the other end of thelight path 6 to receive thelight 4, 5 transmitted through/reflected by/from thesample receiving portion 7/7. Thesample receiving portion 7 is arranged to receive a sample 9 to be analysed for the presence of a target analyte.

Examples of transmission-sideanalytical test devices 1 are described in detail in uk patent application No. 1616301.6, the contents of which are incorporated herein by reference. A brief discussion of certain characteristics of the transmitting sideanalytical test device 1 should be helpful in understanding the present invention.

Each firstoptical transmitter 2 is configured to transmit at a first wavelength λ₁Light 4 in the surrounding range, and eachsecond light emitter 3 is configured to emit light at a second wavelength λ₂Light in the surroundingarea 5. Thefirst light emitter 2 may be in the form of an organic light emitting diode or an inorganic light emitting diode. Similarly, thesecond light emitter 3 may be in the form of an organic light emitting diode or an inorganic light emitting diode. The analytical test device may comprise a plurality offirst light emitters 2 and secondlight emitters 3 arranged in an array.

One ormore photo detectors 8 at least at a first wavelength λ₁And a second wavelength lambda₂Is sensitive over a wide wavelength range. Thephotodetector 8 may be in the form of an organic photodiode or an inorganic photodiode. The emission-sideanalytical test device 1 may comprise a plurality oflight detectors 8 arranged in an array, however, eachlight detector 8 in the array has the same wavelength sensitivity.

Thesample receiving portion 7 of theoptical path 6 may be configured to receive a sample 9 in the form of a lateral flow test strip, a lateral flow test cartridge, a cuvette, a detection (PCR) well/plate, a channel, or a microfluidic device.

Selecting a first wavelength lambda₁And a second wavelength lambda₂Such that the target analyte is specific to the first wavelength λ₁Is lower than the absorbance of the target analyte to the second wavelength lambda₂Is relatively stronger and vice versa. The absorbance of the target analyte itself may not be decisive, e.g. the absorbance of labeled particles of an immunoassay test bound to the target analyte may instead result in the selection of the first wavelength λ₁And a second wavelength lambda₂The basis of (1).

The first 2 and second 3 light emitters are illuminated alternately and the corresponding first signal I₁And a second signal I₂Is detected by thelight detector 8. First signal I₁And a second signal I₂Is converted to a first wavelength lambda₁Absorption Rate A₁And at a second wavelength λ₂Absorption Rate A₂. To calculate the absorption rate value A₁、A₂The signal ofreference light detector 8 may be obtained, for example, by alternately illuminatingfirst light emitter 2 and secondlight emitter 3 in the absence of sample 9 or using a calibration sample that does not contain the target analyte.

Obtaining the absorption rate value A₁、A₂Can be subtracted or removed from the difference, or the difference in weight, of the background inhomogeneity in the sample (excluding the target analyte). This difference appears as a change in absorbance (also referred to as a change in "optical density"). This improves the minimum amount of target analyte that can be detected by theanalytical test device 1. The effect of reducing background non-uniformity for sample 9 is described below (fig. 5-10).

However, the embodiment of the transmission-sideanalytical test device 1 described in british patent application No. 1616301.6 requires alternating illumination of thefirst light emitter 2 and thesecond light emitter 3. This does not allow for the first wavelength λ₁And a second wavelength lambda₂Continuous and simultaneous monitoring.

The transmission-sideanalytical test device 1 described in british patent application No. 1616301.6 requires that the normalized spatial intensity distributions of thelight 4, 5 emitted by each of the first and secondlight emitters 2, 3 should be substantially equal over the sample-receivingportion 7 of thelight path 6.

For example, referring to FIG. 2, if the sample-receivingportion 7 is at a first point x_AAnd a second point x_BOver a distance in a first direction x and at a first point y_AAnd a second point y_BOver a distance (not shown) in the second direction y, the normalizedspatial intensity 10 of the light 4 emitted by thefirst emitter 2 should be substantially equal to the normalizedspatial intensity 11, i.e. x, of the light 5 emitted by thesecond emitter 3 at the entrance surface of thesample receiving portion 7_A≤x≤x_BAnd y_A≤y≤y_B。

In fact, one example of a configuration that can obtain the light uniformity required by the emission-sideanalytical test device 1 is to use an array of first 2 and second 3 emitters in the form of bottom-emitting organic light-emitting diodes (OLEDs), said first 2 and second 3 emitters being coupled with respective filters provided on the back of a transparent substrate. The array offirst emitters 2 andsecond emitters 3 may be a checkerboard array, but in a preferred emission-sideanalytical test device 1, thefirst emitters 2 andsecond emitters 3 are interleaved. In order to reduce or avoid cross-talk between the closely spacedfirst emitter 2 andsecond emitter 3, the transparent OLED substrate must be as thin as possible. Desirably, the substrate thickness is about 100 μm or less, which makes the glass substrate difficult to utilize and prone to mechanical breakage. It has been found that plastic substrates result in poor quality OLED devices with increased noise, reduced lifetime and repeatability (fig. 23 and 24).

The receiving-side differential analysis test apparatus described in this specification can avoid the above-described problems of the transmitting-sideanalysis test apparatus 1, among other advantages.

Receiving side differentiation analysis testing device

As described above, the emission-side differentialanalysis testing device 1 uses two different types of alternately illuminatedlight emitters 2, 3 to obtain a pair of signals for reducing or eliminating background non-uniformities of the sample 9.

In contrast, the receiving-side differentiation analysis test apparatus described in the present specification uses a white, multi-color, or broad-band light emitter to illuminate the sample 9 and two types of light detectors with different wavelength sensitivities to obtain a pair of signals for reducing or eliminating background non-uniformity of the sample 9.

Referring to fig. 3, a firstanalytical test device 12 is shown.

The firstanalytical test device 12 includes one or morelight emitters 13, one or morefirst light detectors 14, one or more secondlight detectors 15, and acalibration module 16.

The one or moreoptical transmitters 13 are each configured to transmit a first wavelength range Δ λ_aThe light inside. A first wavelength range DeltaLambda_aThe light emission within need not be uniform and is generally not uniform. For example, the emission light of the light emitter 13The spectrum may be a continuous broad band spectrum or the emission spectrum of thelight emitter 13 may comprise two or more peaks, which more or less overlap. The one or morelight emitters 13 are white or polychromatic light emitters, such as broad band or multiband emitters, instead of narrow band emitters. Herein, reference to a white orbroadband light emitter 13 shall also refer to apolychromatic light emitter 13. Eachfirst photodetector 14 is paired with a first wavelength λ₁A second surrounding wavelength range Δ λ_bAnd (4) sensitivity. Each second photo-detector 15 pair of second wavelengths lambda₂A third surrounding wavelength range Δ λ_cAnd (4) sensitivity. First wavelength lambda₁And a second wavelength lambda₂Different and all within a first range Δ λ_aAnd (4) the following steps. In other words, the first wavelength λ₁And a second wavelength lambda₂Satisfy the relation: min (Delta lambda)_a)≤λ₁≤max(Δλ_a)，min(Δλ_a)≤λ₂≤max(Δλ_a) And λ₁≠λ₂. Second range DeltaLambda_bOr a third range Δ λ_cMay lie in a first range Δ λ_aAnd (c) out. Second range DeltaLambda_bAnd a third range Δ λ_cNot significantly overlapping. Preferably, the second range Δ λ_bAnd a third range Δ λ_cIs minimized. For example, in a second range Δ λ_bAnd a third range DeltaLambda_cIn any overlapping range therebetween, the sensitivity of thefirst photodetector 14 and/or thesecond photodetector 15 may be less than 3 dB.

The firstanalytical test device 12 is configured such thatlight 17, 18 from one or morelight emitters 13 reaches thefirst light detector 14 and the secondlight detector 15 via a light path (not labeled in fig. 3) comprising thesample receiving portion 7. The optical paths are arranged such that, in response to a sample 9 disposed in thesample receiving portion 7, the first and secondlight detectors 14,15 receive substantially equal amounts of light scattered from each portion of the sample 9 within thesample receiving portion 7. Thus, eachfirst photodetector 14 receives light over a second wavelength range Δ λ_bCorresponding light 17 and a third wavelength range Δ λ_cCorresponding light 18. However, the firstlight detectionThe device 14 generates a second wavelength range DeltaLambda_bThe correspondinglight 17 is responsive to a signal corresponding to a third wavelength range Δ λ_cThe correspondinglight 18 produces no or minimal response from thefirst light detector 14. Similarly, the response of the secondlight detector 15 is subject to a third wavelength range Δ λ_cThecorresponding incident light 18 dominates, although the secondlight detector 15 receives light corresponding to the second wavelength range Δ λ_bCorresponding light 17 and a third wavelength range Δ λ_cCorresponding light 18.

Thecorrection module 16 receives afirst signal 19 from thefirst photodetector 14 corresponding to the incident intensity oflight 17, the light 17 corresponding to a second wavelength range Δ λ_b. Similarly, thecorrection module 16 receives asecond signal 20 from thesecond photodetector 15 corresponding to the incident intensity oflight 18, the light 18 corresponding to a third wavelength range Δ λ_c. Thecorrection module 16 generates acorrection signal 21 based on the difference in the weights of thesignals 19,20 received from the first and secondlight detectors 14, 15. Thecorrection module 16 may comprise a microprocessor or microcontroller configured to generate acorrection signal 21 and optionally convert the output of the light detector to an absorbance value. Alternatively,correction module 16 may include analog circuitry configured to generatecorrection signal 21. For example, the correction module may include an amplification adder circuit 79 (fig. 19) configured to generate thecorrection signal 21 based on the first andsecond signals 19,20 received from the first andsecond photodetectors 14, 15.

In some examples,correction module 16 may include both: an analog circuit configured to generate thecorrection signal 21, and a further microprocessor or microcontroller configured to perform additional functions, such as converting the output of the light detector to an absorbance value.

As further described with reference to fig. 5-10, the effects of background non-uniformities in the material of sample 9 may be reduced or eliminated incorrection signal 21. This may improve the minimum detectable amount of target analyte. The resolution of determining the concentration of the target analyte may also be improved.

In addition, and unlike the emission-side differentialanalysis test device 1, thesignals 19,20 from the first andsecond photodetectors 14,15 can be measured simultaneously using the firstanalysis test device 12. This may allow the correction to be implemented using analog circuitry, which may improve the speed and/or accuracy of the correction. In addition, the sample 9 may be continuously scanned by thesample receiving portion 7. When using the emission side differentialanalysis test device 1, the sample motion must be stopped to allow the same position to be illuminated with the first and secondlight emitters 2, 3, otherwise the measurement results will be related to slightly different positions on the sample 9, resulting in a corresponding decrease in the effectiveness of performing the background subtraction.

Furthermore, any fluctuations/spikes in the output of thelight emitter 13 between thefirst light detector 14 and the secondlight detector 15 will be correlated and thus eliminated by obtaining the difference. As shown in fig. 1, the transmission-side differentiationanalysis test device 1 cannot correct for any such real-time fluctuations in the outputs of thelight emitters 2, 3.

Another advantage is that the sample 9 can be illuminated and measurements of thefirst signal 19 and thesecond signal 20 obtained continuously, since there is no need to alternate between multiple types of light emitters. This allows the use of increased integration time, thereby further reducing the signal-to-noise ratio of the measurement.

Thelight emitter 13 may be any type of light emitter capable of providing white light or light across a relatively wide wavelength range, such as a tungsten filament bulb, a halogen bulb, a fluorescent tube, an inorganic Light Emitting Diode (LED) or an Organic Light Emitting Diode (OLED). A planar array of LEDs or OLEDs arranged close to thesample receiving portion 7 can provide good illumination uniformity across thesample receiving portion 7. Preferably, thelight emitter 13 is in the form of a single,uniform light emitter 13, e.g. a large area uniform white OLED. Preferably, thelight emitter 13 is at least co-extensive (co-extensive) with thesample receiving portion 7.

In some examples, the uniformity of illumination of the first and secondlight detectors 14,15 may be enhanced by arranging the number offirst light detectors 14 and the number of second light detectors 15 (or portions thereof) to form an alternating pattern. The size of eachalternative light detector 14,15 (or part thereof) is smaller than the area of thesample receiving portion 7 projected onto thelight detector 14, 15.

Optionally, in some examples, the light path of the firstanalytical test device 12 further includes alight diffuser 22 disposed between thesample receiving portion 7 of the light path and the first and secondlight detectors 14, 15. This may enhance or further enhance the uniformity of illumination of the first and secondlight detectors 14, 15.

Thefirst photodetector 14 and thesecond photodetector 15 may be in the form of inorganic or organic photodiodes. Eachfirst light detector 14 includes a reference to a second wavelength range a λ_bThe first photosensitive material being sensitive, and each secondlight detector 15 comprising a detector for a third wavelength range Δ λ_cA sensitive second photosensitive material. The photosensitive material may be a blend or mixture of two or more materials. For example, the photoactive material may be a blend of n-type and p-type organic conductors. In this way, the first andsecond photodetectors 14,15 may be inherently or inherently sensitive to different wavelength ranges by including different photosensitive materials.

Thecorrection signal 21 can be generated in a number of ways, depending mainly on the optical path, the number, type and geometry of the first andsecond photodiodes 14,15 and thelight emitters 13.

If theoptical emitter 13 andoptical detectors 14,15 are relatively uniform, flat and parallel, such that the optical path and thesample receiving portion 7 effectively exhibit a cubic gap between theoptical emitter 13 andoptical detectors 14,15, thecorrection signal 21 can be determined according to the following general formula:

wherein I_CTo correct the signal, I¹_nIs the signal from the nth one of the N first photo-detectors 14, I²_nFor the signal from the nth of the N second photodetectors, α is a predetermined weight factor, N is a real positive integer satisfying N ≧ 1.

Alternatively, if the geometry of theoptical emitter 13, the optical path, and the first and secondoptical detectors 14,15 is complex, different coefficients may be applied to the signals corresponding to eachoptical detector 14,15 according to:

β therein_nIs a weighting factor, γ, corresponding to the nth of the Nfirst photodetectors 14_nIs the weighting factor corresponding to the nth of the N second photo-detectors 15.

Sample 9 is not limited to any particular form. For example, thesample receiving portion 7 of the optical path may be configured to receive a sample 9 in the form of a lateral flow test strip 23 (FIG. 4). Alternatively, thesample receiving portion 7 of the optical path may be configured to receive a sample 9 in the form of: cuvettes (fig. 26), assay well plates (fig. 27), channels (fig. 28), portions of microfluidic devices (fig. 29), and the like.

The sample 9 may simply be placed within thesample receiving portion 7, for example resting on thelight emitter 13. Alternatively, the firstanalytical test device 12 may also include a sample mounting stage 24 (fig. 4) which is movable between a loading position and one or more measurement positions in which all or part of the mounted sample 9 is placed in thesample receiving portion 7 of the optical path. In the loading position, sample mounting stage 24 (FIG. 4) is configured to enable a sample to be easily placed and/or secured to or in or within sample mounting stage 24 (FIG. 4). In some examples, a drive device, such as a motor, may be provided to move thesample mount 24 between the loading position and the measurement position (fig. 4). Additionally or alternatively, the drive means can cause the sample 9 to be scanned through thesample receiving portion 7, for example, to scan along the length of the lateral flow test strip 23 (fig. 4).

Lateral flow test strip reader

One example application of the firstanalytical test device 12 is as part of a lateral flowtest strip reader 25.

Referring also to FIG. 4, a portion of lateral flowtest strip reader 25 is shown that includes firstanalytical test device 12.

Lateral flow test strips 23 (also referred to as "lateral flow immunoassays") are various biological detection kits. The lateralflow test strip 23 may be used to test a liquid sample (e.g., saliva, blood, or urine) for the presence of an analyte. Examples of such lateral flow devices include home pregnancy tests, home ovulation tests, tests for other hormones, tests for specific pathogens, and tests for specific drugs.

Lateral flowtest strip reader 25 includes firstanalytical test device 12 andsample mounting block 24. Thesample mounting stage 24 includes aflat base 26 surrounded by alip 27 which projects perpendicularly from thebase 26. Theflat base 26 is rectangular, and thebase 26 andlip 27 are shaped and dimensioned to be able to receive the lateralflow test strip 23 supported by the base 26 against gravity, such that thelip 27 substantially prevents the lateralflow test strip 23 from shifting when thesample mounting station 24 is moved. Theflat base 26 includes a substantiallyrectangular window 28. Thewindow 28 has a long axis aligned with the long axis of therectangular base 26. Thus, light 17, 18 fromlight emitter 13 may pass throughwindow 28 to illuminate lateralflow test strip 23.Light 17, 18 transmitted through the lateralflow test strip 23 is detected by first and secondlight detectors 14,15 (not shown in fig. 4) as described above.

The lateralflow test strip 23 includes one ormore test areas 29. Optionally, the lateralflow test strip 23 can also include one ormore control zones 30, e.g., onecontrol zone 30 corresponding to eachtest zone 29. Thesample mount 24 translates through thesample receiving portion 7 of the optical path to obtain a scan of the lateralflow test strip 23. In this way, the absorbency of eachtest area 29 and/or eachcontrol area 30 can be measured. Alternatively, if the positional alignment of the lateralflow test strip 23, thetest area 29 and theoptional control area 30 is sufficiently precise, thesample mounting stage 24 can be moved directly to a preset position in which thetest area 29 orcontrol area 30 of interest is located within thesample receiving portion 7 of the optical path.

Thesample mounting stage 24 is manually movable. Preferably, thesample mounting station 24 is connected to a drive mechanism (not shown) that scans the lateralflow test strip 23 through thesample receiving portion 7, or the drive mechanism is used to position the lateralflow test strip 23 in one or more predetermined positions. The drive means (not shown) may be of the form: such as a motor, hydraulic actuator or pneumatic actuator.

Thesample mounting station 24 is only one example of a sample mounting station, and other configurations that use different means to hold and/or secure the lateralflow test strip 23 to theflat base 26 andlip 27 may be used.

Correction of background inhomogeneity of a sample

Referring also to fig. 5, a simplified lateralflow test strip 23 is shown.

The lateralflow test strip 23 extends longitudinally in a first direction x, laterally in a second direction y, and has a thickness in a third direction z. Atest zone 29 is defined between positions B and B' in the first direction x.

In a typical lateralflow test strip 23, a liquid sample is introduced at one end of theporous strip 31 and then drawn along the lateralflow test strip 23 by capillary action (or "wicking"). Theporous strip 31 is pre-treated with label particles 32 (fig. 6), and if analyte is present in the liquid sample, the label particles 32 are activated by the reagent that binds to the analyte to form a complex. The bound complex and unreacted labeling particles 32 (fig. 6) continue to propagate along the lateralflow test strip 23 before reaching thetest area 29.Test area 29 is pretreated with an immobilized binding reagent that binds to the complex of analyte bound to label particles 32 (fig. 6), but not to unreacted label particles 32 (fig. 6). Marking particles 32 (fig. 6) have a unique color or otherwise absorb one or more ranges of ultraviolet, visible, infrared, or near-infrared light. The development of the concentration of the marking particles 32 (fig. 6) in thistest area 29 can be measured and quantified using the firstanalytical test device 12, for example by measuring the absorbance caused by the marking particles 32 (fig. 6). The firstanalytical test device 12 can perform a measurement on a developed lateralflow test strip 23, i.e., a liquid sample has been placed for a preset period of time to be drawn along thetest strip 23.

Alternatively, the firstanalytical test device 12 may perform a kinetic, i.e. dynamic time-resolved measurement of the optical density of the labeling particles 32 (fig. 6). The firstanalytical test device 12 is particularly suitable for dynamic time-resolved measurements, since the first and secondlight detectors 14,15 can be monitored simultaneously and continuously.

Referring also to FIG. 6, the structure of theporous strip 31 of the lateralflow test strip 23 is shown.

Theporous strip 31 is typically formed from a mat offibers 33, such as nitrocellulose fibers. Within thetest zone 29, the immobilized binding reagent binds the analyte and the complex of labeled particles 32.

Thefibers 33 scatter and/or absorb light across a wide range of wavelengths in an approximately similar manner. For example, scattered by thefiber 33 corresponding to the second wavelength range Δ λ_bIs proportional to the light corresponding to the third wavelength range a λ_cIs approximately the same. However, the fibrousporous strip 31 is not uniform, and the density of thefibers 33 may vary from point to point within theporous strip 31. As explained further below, such background variations in absorbance caused by non-uniformity of theporous strip 31 may limit the sensitivity of the measurement, i.e. the minimum detectable concentration of labeled particles 32.

Referring also to fig. 7, anidealized absorption spectrum 34 of the marker particles 32 used in the lateralflow test strip 23 is shown.

Provided that the first and second wavelengths λ of the labeling particles 32 used in the lateralflow test strip 23 are appropriately selected₁、λ₂And corresponding second and third wavelength ranges Δ λ_b、Δλ_cThe firstanalytical test device 12 may compensate for such background variations in absorbance due to non-uniformities of theporous strip 31. For example, anabsorption spectrum 34 of marking particles 32 may be obtained to determine how the absorbance of marking particles 32 varies with wavelength/frequency. Select the firstA wavelength λ₁And a corresponding second wavelength range delta lambda_bAt or near the peak absorbance of the marking particles 32. Selecting a second wavelength lambda₂And a corresponding third wavelength range Δ λ_cSo as to be at a wavelength remote from the peak absorbance of the marking particles 32. In other words, the first wavelength and the second wavelength λ are selected₁、λ₂And corresponding second and third wavelength ranges Δ λ_b、Δλ_cSuch that marking particles 32 are in a second wavelength range Δ λ_bIs relatively higher than in the third wavelength range Δ λ_cIs used in the preparation of the medicament. First wavelength lambda₁And a second wavelength lambda₂The ratio of absorbance between can be, for example, a factor of at least 1.5, at least 2.0, up to and including 5.0, up to and including 10.0, up to and including 20.0, or greater than 20.0.

First wavelength lambda₁And a second wavelength lambda₂May lie in a range between 300nm and 1500nm, inclusive. First wavelength lambda₁And a second wavelength lambda₂May lie in a range between 400nm and 800nm, inclusive.

With particular reference to FIG. 6, in addition to being absorbed and/or scattered by thefibers 33, a second wavelength range Δ λ_bThe correspondinglight 17 is also absorbed and/or scattered by the marking particles 32. In contrast, a third wavelength range Δ λ_cThe correspondinglight 18 interacts only weakly or not at all with the marker particles 32.

Referring also to fig. 8-10, the generation of thecorrection signal 21 is shown.

The lateralflow test strip 23 may be passed through thesample receiving portion 7 of the exemplary optical path of the firstanalytical test device 12, for example, using the lateral flowtest strip reader 25, and the measured absorbance value a (x) is a function of the position x of theporous strip 23 along the lateralflow test strip 23. When the sample 9 (in this case, the lateral flow test strip 23) occupies thesample receiving portion 7 and a reference state (e.g., no sample 9 or a calibration sample without labeled particles present), an absorbance value a (x) is determined based on the difference in transmittance or reflectance.

First absorption A₁(x) ByThefirst light detector 14 measures and correlates with the second wavelength range Δ λ_bAnd correspondingly. Similarly, the second absorption A₂(x) Measured by the secondlight detector 15 and associated with a third wavelength range Δ λ_cAnd correspondingly. First and second absorption A₁(x)、A₂(x) With substantially equal contributions from scattering and/or absorption by thefibres 33 of theporous strip 31. The background level of absorbance varies with position x along theporous strip 31 due to non-uniformity in the density of thefibers 33. The absorbance signals caused by the marking particles 32 cannot be reliably detected unless they are at least larger than the background differences caused by the inhomogeneities of theporous strip 31. This limits the lower limit of the concentration of label particles that can be detected using the lateralflow test strip 23. The same background variation also limits the resolution of the quantitative measurement of the concentration/optical density of the marking particles 32.

However, since thefibers 33 scatter the second and third wavelength ranges Δ λ in substantially the same manner_b、Δλ_cInternal light, and therefore can be extracted from the first absorption value A₁(x) Minus the second absorption value A₂(x) To reduce or eliminate the effects of background absorbance changes caused by the uneven distribution offibers 33 in the porous strip, in effect, the differences are weighted by a weighting factor α, as in equation (1), such that:

A_C(x)＝A₁(x)-αA₂(x) (4)

wherein A is_C(x) Corresponding to acorrection signal 21 in the form of a corrected absorbance value. Value A_C(x) Corresponding to the change in absorbance attributable to the marking particles 32. Alternatively, the first andsecond signals 19,20 output by the first and second photo-detectors 14,15 may be directly corrected, and thecorrection module 16 may then correct the corrected signal I, as described with respect to equations (1) to (3)_C(x) Conversion into a change in absorbance attributable to the labeled particles A_C(x)。

Although in practice, when the difference A is obtained₁(x)-αA₂(x) Some amount of background change in absorbance is retained, but the relative magnitude of the signal characteristic of the marking particle 32 may be increased (in some cases significantly increased) relative to the background change. In this way, the lower limit of the concentration of the labeling particles 32 that can be detected can be lowered. Similarly, the resolution of the quantitative measurement of the concentration/optical density of marker particles 32 may be increased.

Organic photodetector

Referring also to fig. 11 and 12, the layer structure of exemplary Organic Photodetectors (OPDs) 35, 36 is shown.

With particular reference to fig. 11, the firstanalytical test device 12 may include afirst photodetector 14 and asecond photodetector 15 in the form of abottom absorption OPD 35.

The exemplarybottom absorbing OPD 35 comprises a layer structure comprising atransparent substrate 37 arranged in the thickness direction z, atransparent anode layer 38 comprising one or more anode electrodes, ahole transport layer 39, a photo sensitive OPDactive layer 40, areflective cathode layer 41 comprising one or more cathode electrodes. The OPDactive layer 40 is in the form of a blend of n-type and p-type organic semiconductors. Optionally, depending on the material or materials used for the OPDactive layer 40, thebottom absorbing OPD 35 may further comprise an electron transport layer 42 (sometimes also referred to as a "hole blocking" layer) disposed between the OPDactive layer 40 and thereflective cathode layer 41. Anencapsulant layer 43 typically covers thereflective cathode 41 to protect thebottom absorbing OPD 35 from moisture that may be harmful to some or all of the materials forming thebottom absorbing OPD 35.

By selecting different materials for the OPDactive layers 40 of the first andsecond photodetectors 14,15, the first andsecond photodetectors 14,15 in the form ofbottom absorption OPDs 35 may be arranged to pair the respective second and third wavelength ranges Δ λ_b、Δλ_cAnd (4) sensitivity.

With particular reference to fig. 12, the firstanalytical test device 12 may include afirst photodetector 14 and asecond photodetector 15 in the form of atop absorption OPD 36.

The exemplarytop absorbing OPD 36 comprises a layer structure comprising asubstrate 44 arranged in a thickness direction z, atransparent cathode layer 45 comprising one or more cathode electrodes, an electron modification layer 46 (sometimes also referred to as "electron extraction layer"), an OPDactive layer 47 sensitive to light, ahole transport layer 48, and a transparent orsemi-transparent anode layer 49 comprising one or more anode electrodes. Theelectron modifying layer 47 is provided to change the work function of thecathode layer 45, for example Indium Tin Oxide (ITO), so as to make the work function of thecathode layer 45 and theelectron modifying layer 46 as a whole shallower. The OPDactive layer 47 is in the form of a blend of n-type and p-type organic semiconductors. Optionally, areflective layer 50 may be disposed between thecathode layer 45 and thesubstrate 44. Anencapsulant layer 51 typically covers theanode layer 49 to protect thetop absorbing OPD 36 from moisture that may be harmful to some of all of the materials forming the top absorbingOPD 36.Substrate 44 may be transparent or translucent, although this is not required for top absorbingOPD 36.

The first andsecond photodetectors 14,15 in the form oftop absorption OPDs 36 may be configured to couple the respective second and third wavelength ranges Δ λ by selecting different materials for the OPDactive layers 47 of the first andsecond photodetectors 14,15_b、Δλ_cAnd (4) sensitivity.

Receiving side differential analysis testing device using filter

Since the first and secondlight detectors 14,15 comprise different light-sensitive materials, the first and secondlight detectors 14,15 of the firstanalytical test device 12 are paired with respective second and third wavelength ranges Δ λ_b、Δλ_cAnd (4) sensitivity. However, it is not essential that different photosensitive materials are used for the first and secondlight detectors 14, 15.

Referring also to fig. 13, a secondanalytical test device 52 is shown.

The secondanalytical test device 52 is identical to the firstanalytical test device 12, except that the first andsecond photodetectors 14,15 comprise the same photosensitive material. For example, when the first andsecond photodetectors 14,15 are in the form ofbottom absorbing OPDs 35 or top absorbingOPDs 36, then theOPDs 35, 36 may comprise the same OPDactive layer 40, 47.

To provide corrected wavelength sensitivity, the secondanalytical test device 52 includes afirst filter 53 corresponding to or incorporated in eachfirst light detector 14 and a second filter corresponding to or incorporated in each second light detector 15Two filters 54. Eachfirst filter 53 is arranged to filter light 17, 18 arriving from thesample receiving portion 7 via the optical path before the light 17, 18 reaches the photosensitive material of the respectivefirst light detector 14. Eachfirst filter 53 is configured to transmit a second range of wavelengths Δ λ_bCorresponding light 17, and corresponding to a third wavelength range Δ λ_cThe correspondinglight 18 is attenuated. Similarly, eachsecond filter 54 is arranged to filter light 17, 18 arriving from thesample receiving portion 7 via the optical path before the light 17, 18 reaches the photosensitive material of the respective secondlight detector 15. Eachsecond filter 54 is configured to transmit light over a third wavelength range Δ λ_cCorresponding light 17, and corresponding to a second wavelength range Δ λ_bThe correspondinglight 18 is attenuated.

Eachfirst filter 53 may be integrated into a respectivefirst light detector 14 and eachsecond filter 54 may be integrated into a respective secondlight detector 15. For example, each first light detector may include a photosensitive material and afirst filter 53, and each second light detector may include a photosensitive material and asecond filter 54. Alternatively, thefilters 53, 54 may be provided as separate layers covering the first and secondlight detectors 14, 15.

When the first andsecond photodetectors 14,15 are in the form ofbottom absorbing OPDs 35, the first andsecond filters 53, 54 may be disposed on the opposite side of thetransparent substrate 37 from theanode layer 38, for example by printing colored inks.

When the first andsecond photodetectors 14,15 are in the form of a top absorbingOPD 36, the first andsecond filters 53, 54 may be disposed over theencapsulation layer 51, for example, by printing colored inks. Alternatively, the first andsecond filters 53, 54 may be provided over theanode layer 49, and theencapsulating layer 51 may be disposed over the first andsecond filters 53, 54. In another alternative, theenvelope layer 51 itself may incorporate the first andsecond filters 53, 54 integrally, for example, theenvelope layer 51 may be in the form of a single sheet of transparent polymeric film that has been dyed or otherwise treated so that different areas are differently colored.

Referring also to fig. 14A and 14B, a firstexemplary layout 55 of thephotodetectors 14,15 and filters 53, 54 of the secondanalytical test device 52 is shown.

With particular reference to fig. 14A, eachfirst light detector 14 comprises aridge 56 extending in the first direction x and a plurality ofbranches 57 extending from theridge 56 in the second direction y. Similarly, each secondlight detector 15 comprises aridge 58 extending in the first direction x and a plurality ofbranches 59, saidbranches 59 extending from theridge 58 in the second direction y and having the opposite meaning to thebranches 57 of thefirst light detector 14. Each pair of first and secondlight detectors 14,15 is arranged such that therespective branches 57, 59 are interleaved.

Referring now specifically to fig. 14B, the respective first andsecond filters 53, 54 are arranged in respective staggered, interdigitating arrangements.

In this way, the difference in the amount oflight 17, 18 incident on the first andsecond photodetectors 14,15 can be reduced. The uniformity of illumination of the first and secondlight detectors 14,15 may be further improved when anoptional diffuser 22 is included in the light path between thesample receiving portion 7 and thelight detectors 14, 15.

The use of interleavedbranches 57, 59 is not required, and in an alternative example, the plurality offirst light detectors 14 may be elongated in the first direction x, and the plurality of secondlight detectors 15 may be elongated in the first direction x, and the first and secondlight detectors 14,15 may be interleaved in the second direction y.

Referring also to FIG. 15, emission and absorption characteristics corresponding to one exemplary combination oflight emitter 13 and filters 53, 54 for measuring marking particles 32 are shown.

The normalized absorbance 60 (solid line in fig. 15) of the labeling particles 32 corresponds to the labeling particles 32 in the form of 40nm gold nanoparticles. Such gold nanoparticles may be used as the labeling particles 32 in a lateralflow test strip 23 system. The normalizedemission spectrum 61 of the OLED (dashed line in fig. 15) is also shown for reference. It can be observed that the goldnanoparticle absorption spectrum 60 shows a peak absorption around green wavelengths, and a relatively weak absorption around red wavelengths. In this example, a second wavelength range Δ λ may be selected_bCorresponds to greenColor wavelength, and a third wavelength range Δ λ can be selected_cCorresponding to the red wavelength. FIG. 15 shows a normalized absorption spectrum 62 (dotted line in FIG. 15) of afirst filter 53 in the form of a green filter transmitting a second wavelength range Δ λ of about 400nm to about 600nm_b. FIG. 15 also shows a normalized absorption spectrum 63 (dotted line in FIG. 15) of thesecond filter 54 in the form of a red filter that transmits a third wavelength range Δ λ from about 600nm to the Near Infrared (NIR)_c。

Thus, when gold nanoparticles are present in thesample receiving portion 7, thefirst light detector 14 will detect a strong change in absorbance, while the response of the secondlight detector 15 to the gold nanoparticles will be small or negligible. In contrast, thefibers 33 that make up theporous strip 31 of the lateralflow test strip 23 are typically white or substantially white, such that the response of the first and secondlight detectors 14,15 to thefibers 33, and any non-uniformities thereof, will correlate. Thus, by obtaining the above-described differences (equations (1) through (4)), the effects of background non-uniformity of thefibers 33 may be reduced or eliminated.

Referring also to fig. 16A, a secondexemplary layout 64 of thephotodetectors 14,15 and filters 53, 54 of the secondanalytical test device 52 is shown.

In thesecond layout 64, the plurality of first photo-detectors 14 and the plurality of second photo-detectors 15 are arranged in an alternating grid. The respective first andsecond filters 53, 54 are also arranged in an alternating grid.

Thefirst light detector 14 and the correspondingfirst filter 53 are arranged in a first lattice and the secondlight detector 15 and the correspondingsecond filter 54 are arranged in a second lattice. The first and second lattices are identical except that the second lattice is shifted relative to the first lattice such that the first and second lattices interpenetrate. In the example shown in fig. 16A, the first lattice and the second lattice may be regarded as an oblique lattice having a unit cell including asingle filter 53, 54, or as a square lattice having a unit cell including a pattern of a pair offilters 53, 54.

Referring also to fig. 16B, a thirdexemplary layout 65 of thephotodetectors 14,15 and filters 53, 54 of the secondanalytical test device 52 is shown.

Thethird layout 65 is identical to thesecond layout 64, except for the form of the first lattice and the second lattice. In this case, the first lattice and the second lattice are each a square lattice having a unit cell including thesingle filter 53, 54.

Any other suitable pattern of interpenetrating 2D lattices may be used to arrange thephotodetectors 14,15 and filters 53, 54 of the secondanalytical test device 52.

Although the interdigitated arrangement shown in fig. 14A and 14B and the interpenetrating lattice arrangement shown in fig. 16A and 16B have been described with respect to the secondanalytical test device 52, the same or similar arrangement of the first andsecond photodetectors 14,15 may be employed in the firstanalytical test device 12 in order to enhance the uniformity of illumination of the first andsecond photodetectors 14, 15.

Receiving side differential analysis testing device using resonant cavity

Referring also to fig. 17, the layer structure of the modified top absorbing OPD66 is shown.

A third analytical test device (not shown) is identical to the secondanalytical test device 52, except that the first andsecond filters 53, 54 are not used, and the third analytical test device uses a modified top absorption OPD66 that includes aresonant microcavity 75 that can be tuned to enhance absorption at the desired wavelength.

The modified top absorbing OPD66 includes asubstrate 68 having areflective cathode 69 disposed thereon. A transparentconductive oxide layer 67 is disposed on thereflective cathode 69, and anelectron transport layer 70 is disposed on the transparentconductive oxide layer 67. The transparentconductive oxide layer 67 may be in the form of, for example, Indium Tin Oxide (ITO). The transparentconductive oxide layer 67 and theelectron transport layer 70 together constitute a two-layer stack. An OPDactive layer 71 is disposed on the bilayer stack. The OPDactive layer 71 is in the form of a blend of n-type and p-type organic semiconductors. The hole transport layer 72 is disposed between and in electrical contact with the OPDactive layer 71 and thetranslucent anode layer 73. Anencapsulant layer 74 is provided to cover theanode layer 73 and surround the modified top absorbing OPD66 to prevent or slow the ingress of moisture that may have a deleterious effect on some or all of the materials of the modifiedtop absorbing OPD 66. Amicrocavity 75 is formed between thetranslucent anode layer 73 and thereflective cathode 69.

The improved top absorption OPD66 exhibits a favorable light response, which enables efficient and efficient color resolution, since a particularly narrow full width at half maximum (FWHM) and a high External Quantum Efficiency (EQE) value can be obtained simultaneously, so that wavelength sensitivity can be improved without using an optical filter. Thus, the third analytical test device does not comprise the first andsecond filters 53, 54.

It has been surprisingly found that the resonance wavelength of themicrocavity 75 can be changed not only by changing the thickness of the OPDactive layer 71, but also by changing the total thickness of the transparentconductive oxide layer 67 and the OPDactive layer 71, the OPDactive layer 71 comprising a blend of an n-type organic semiconductor and a p-type organic semiconductor. In this way, it is possible to set the thickness of the OPDactive layer 71 to an optimized value in terms of EQE efficiency, processability, etc., and then adjust the resonant wavelength of themicrocavity 75 by adjusting the thickness of theconductive oxide layer 67 without substantially affecting the improved top absorption OPD66 performance.

Preferably, the n-type organic semiconductor and the p-type organic semiconductor blended to form the OPDactive layer 71 are selected such that the OPDactive layer 71 is at the target wavelength λ_maxExhibits a transmission T of at least 50%, the target wavelength lambda_maxIs the maximum wavelength of the External Quantum Efficiency (EQE) spectrum of the improved top absorption OPD66 in the desired range as measured from astm e 1021. For example, for thefirst photodetector 14, the wavelength λ_maxShould correspond to the first wavelength lambda₁Or at least at a first wavelength λ₁A second surrounding wavelength range Δ λ_bWithin. The wavelength λ can also be adjusted by changing the thickness of the OPDactive layer 71_max. The thickness of the transparentconductive oxide layer 67 is then adjusted to tune the resonant wavelength of themicrocavity 75 to the desired value λ_max。

The modified top absorbing OPD66 may be fabricated using one or more deposition techniques, such as photolithography, sputtering, thermal deposition, vacuum deposition, laser deposition, screen printing, embossing, spin coating, dip coating, ink jet printing, roll coating, flow coating, drop casting, spray coating, and/or roll printing.

Thus, instead of usingfilters 53, 54, the respective second and third wavelength ranges Δ λ for the first andsecond photodetectors 14,15 are provided by using a modified top absorption OPD66_b、Δλ_cThe improved top absorption OPD66 comprises aresonant cavity 75 with a suitably tuned resonance wavelength. For example, eachfirst photodetector 14 may include a photosensitive material in the form of an OPDactive layer 71, and a firstresonant cavity 75, the firstresonant cavity 75 being configured to correspond to a second wavelength range Δ λ_bIs coupled in to the light 17. Similarly, eachsecond photodetector 15 comprises a photosensitive material in the form of an OPD active layer, and a secondresonant cavity 75, said secondresonant cavity 75 being configured to correspond to a third wavelength range Δ λ_cIs coupled in to the light 18.

Examples of improved top absorption photodetectors

The first, second, and third examples of the improvedtop absorption photodetector 66 were fabricated and evaluated using silver to form asemi-transparent anode layer 73 and areflective cathode 69. The OPDactive layer 71 is formed from a blend of a PCBM type fullerene derivative, in particular phenyl-C61-methyl butyrate (C60PCBM), and a p-type organic semiconductor of structural formula (a):

c60PCBM and compound (a) are characterized by low absorptance around an exemplary target wavelength of 550nm (green), and exhibit absorption maxima at about 430nm (C60PCBM and compound (a)), 720nm (compound (a)), and 800nm (compound (a)). Ensuring that the active layer comprising a blend of C60PCBM and compound (A) is at a target wavelength of 550nm (. lamda.) (λ) at the thickness given in the examples described below_max) Has a transmittance T of at least 50%.

Example 1

As the transparentconductive oxide layer 67, an ITO layer having a thickness of 45nm was deposited on thereflective cathode 69 formed of silver, and the OPDactive layer 71 had a thickness of 160nm, which resulted in a total thickness of the active layer and the conductive oxide layer of 205 nm.

Example 2

An organic photodetector was prepared according to example 1, except that the thickness of the ITO layer was 25 and the thickness of the active layer was 180nm, so that the total thickness of the active layer and the conductive oxide layer was maintained at 205 nm.

Example 3

Additional organic photodetectors were prepared according to example 1, except that the thickness of the ITO layer was 80nm and the thickness of the active layer was 140nm, resulting in a total thickness of the active layer and the conductive oxide layer of 220 nm.

The external quantum efficiency of each of the organic photodetectors of examples 1 to 3 was measured over a wavelength range of about 400 to 700nm using a calibrated incident photon-to-charge carrier efficiency (IPCE) measurement system. FWHM was calculated as the width of the wavelength corresponding to half the maximum EQE using a gaussian fit curve of the central EQE peak.

Referring also to fig. 18, External Quantum Efficiency (EQE)spectral lines 76, 77, 78 are shown for OPDs ofembodiments 1 to 3. Dashed line indicates the voltage V at reverse bias_BEQE response at-1V, with solid curve at V_BEQE response when 0V.

It can be observed that the EQE line 77 (dark grey line in fig. 18) of the OPD of example 2 shows an EQE peak centered at about 510nm with a FWHM of about 40nm and an external quantum efficiency at V_BAbout 26% at-1V, at V_BAbout 23% when it is 0V.

Similarly, it can be observed that the EQE line 76 (light gray line in fig. 18) of the OPD of example 1 also exhibits a peak centered at about 510nm with a FWHM of about 40nm, with a relatively low external quantum efficiency (at V)_BAbout 20% at-1V, at V_BAbout 18% at 0V). It can be observed that, since the thickness of the transparentconductive layer 67 is reduced, when the thickness of the OPDactive layer 71 is increased to 180nm, the resonance wavelength is not significantly shifted, so that the total thickness is the same asembodiment 1.

By contrast, it can be observed that the EQE line 78 (black line in fig. 18) of the OPD of example 3 indicates that increasing the total thickness of the OPDactive layer 71 and the conductivetransparent oxide layer 67 to 220nm shifts the EQE maximum to a longer wavelength (about 535nm), which indicates that when compared to example 1, the resonant wavelength can be adjusted to a desired value by adjusting the thickness of the transparentconductive oxide layer 67 without changing the OPDactive layer thickness 71, and thus has no significant effect on the FWHM and external quantum efficiency (FWHM of about 40nm, at V, at about 40 nm)_BEQE is about 23% when-1V and about 21% when VB is 0V).

Circuit for generating correction signal

Fig. 19 is a circuit diagram of an example of anamplification adder circuit 79 that may be included in thecorrection module 16.

Thecircuit 79 comprises a first input terminal V for receiving thefirst signal 19 from thefirst photo detector 14₁And a second input terminal V for receiving asecond signal 20 from asecond photo detector 15₂. First input terminal V₁Via a first resistor R₁Coupled to an operational amplifier OP₁Is input in the opposite phase. Similarly, the second input terminal V₂Via a second resistor R₂Coupled to an operational amplifier OP₁Is input in the opposite phase. First and second resistors R₁、R₂One terminal of each of which is connected to the inverting input atnode 80. Amplifier OP₁The non-inverting input of (a) is grounded. Thecircuit 79 comprises a feedback resistor R in the form of a feedback resistor_fIs connected to the amplifier OP₁Inverting input and output V of_outIn the meantime. Amplifier output V_outA correction signal 21 is provided. Amplifier output V_outBy a first resistance R₁A second resistor R₂And a feedback resistor R_fIs determined according to the following equation:

in this way, theamplification adder circuit 79 may be used to implement equation (2). In addition, by including coupling by means of corresponding resistances toOther voltage input V ofnode 80₃，…，V_NEquation (1) or (3) can be implemented in the amplifier circuit as well.

In this way, the first, second and/or third receiving-side differentialanalysis test devices 12, 52 can generate thecorrection signal 21 in real time without the need to amplify and convert the input signals 19,20, respectively, into digital data before performing the correction. This may reduce the amount of uncorrelated noise acquired by thesignals 19,20 before the difference is obtained and thus may improve the quality of the correction signal compared to the transmit sideanalytical test device 1 described in uk patent application No. 1616301.6.

Measuring geometry

The first, second and/or thirdanalytical test devices 12, 52 may be configured to use the geometry of a series oflight emitters 13 andlight detectors 14, 15.

Referring also to fig. 20, there is shown an arrangement in which the optical path is arranged such that the first andsecond photodetectors 14,15 receive light transmitted through thesample receiving portion 7.

For transmission measurements, thelight emitter 13 and the light detector may simply be separated by a gap corresponding to the light path. Then, when the sample 9 is received in theanalytical test device 12, 52, thesample receiving portion 7 of the optical path corresponds to the portion of the gap occupied by the sample 9.

For example, if a sample 9 in the form of a lateralflow test strip 23 is used, the lateralflow test strip 23 may be arranged with atest area 29 located between thelight emitter 13 and thelight detectors 14, 15. Thesample receiving portion 7 of the optical path corresponds to the thickness of the lateralflow test strip 23 that intersects the optical path.

Additional optical elements may be included in the optical path. For example, light entering the optical path from thelight emitter 13 and/or light from the optical path to thelight detectors 14,15 may be restricted by a slit or other aperture. Optionally, adiffuser 22 may also be included in the light path between thesample receiving portion 7 and thelight detectors 14, 15.

However, the first, second andthird analysis devices 12, 52 described herein are equally applicable to the measurement of reflectance.

Referring also to fig. 21, there is shown an arrangement in which the optical paths are arranged such that the first andsecond photodetectors 14,15 receive light reflected from thesample receiving portion 7.

For example, whenanalytical test device 12, 52 is arranged to receive sample 9 in the form of lateralflow test strip 23, one or morelight emitters 13 may be arranged at a first angle θ₁A target area of a lateralflow test strip 23 housed in theanalytical test device 12, 52 is illuminated, and alight detector 14,15 may be arranged to receive light reflected from the lateralflow test strip 23. Due to the largely random orientation of thefibers 33, light reflected from theporous strip 31 of thelateral test strip 23 will typically be scattered into a wide range of different angles. Thus, the portion of the optical path between thesample receiving portion 7 and thephotodetectors 14,15 may be at a second angle θ₂Orientation of the second angle theta₂Not necessarily equal to the first angle theta₁. In some examples, the first angle θ₁And a second angle theta₂May be equal. In some examples, thelight emitters 13 andlight detectors 14,15 may be arranged in a confocal optical configuration. The light reflected from sample 9 may originate fromsurface 81 of sample 9 or from a depth within sample 9.

Additional optical elements may be included in the optical path. For example, light entering the optical path from thelight emitter 13 and/or light from the optical path to thelight detectors 14,15 may be restricted by a slit or other aperture. Optionally, adiffuser 22 may also be included in the light path between thesample receiving portion 7 and thelight detectors 14, 15.

Lateral flow device with integrated analytical test device

Referring also to fig. 22, alateral flow device 82 is shown that includes an integrated example of the first, second, or thirdanalytical test devices 12, 52.

The lateralflow test device 82 includes aporous strip 31 that is divided into a sample receiving portion 83, an engaging portion 84, a testing portion 85, and a wickingportion 86. Theperforated strip 31 is received in the seat 87. Acover 88 is attached to the base 87 to secure theperforated strip 31 and cover portions of theperforated strip 31 that are not required to be exposed. Thecover 88 includes asample receiving window 89 that exposes a portion of the sample receiving portion 83 to define a liquidsample receiving area 90. The cover andbase 87, 88 are made of a polymer such as polycarbonate, polystyrene, polypropylene or the like.

The base 87 comprises arecess 91 in which the first and secondlight emitters 13a, 13b are accommodated. Eachlight emitter 13 may be configured as described above. Eachlight emitter 13 may be an OLED, for example a white OLED. Thecover 88 includes arecess 92 in which the first pair of first andsecond photodetectors 14a, 15a and the second pair of first andsecond photodetectors 14b, 15b are housed. Thephotodetectors 14a, 15a, 14b, 15b are preferably in the form of OPDs. Each pair of first and secondlight detectors 14A, 15a, 14b, 15b is preferably interleaved in a similar manner to the second layout 55 (fig. 14A). Thephotodetectors 14a, 15a, 14b, 15b may be inherently aligned to the respective wavelength range Δ λ_b、Δλ_cSensitive (as in the first analytical test device 12), may include or be combined withfilters 53, 54 (as in the second analytical test device 52), or may include a microcavity 75 (as in the third analytical test device).

Thefirst light emitter 13a and the first pair of first and secondlight detectors 14a, 15a are disposed on opposite sides of thetest zone 29 of theperforated strip 31. Thesecond light emitter 13b and the second pair of first and secondlight detectors 14b, 15b are disposed on opposite sides of thecontrol zone 30 of themultiwell strip 31. Aslit member 93 separates thelight emitter 13 from theperforated strip 31 to define aslit 94, theslit 94 extending transversely across the width of theperforated strip 31 and through which slit 94 the first and secondlight emitters 13a, 13b illuminate thetest area 29 and thecontrol area 30, respectively. For example, if theporous strip 31 extends in the first direction x and has a thickness in the third direction z, theslit 31 extends in the second direction y. Thefurther slit member 95 defines aslit 96, which slit 96 separates thelight detectors 14a, 15a, 14b, 15b from theporous strip 31. Theslits 94, 96 may be covered by a thin layer of transparent material to prevent moisture from entering therecesses 91, 92. A material can be considered transparent to a particular wavelength λ if it transmits greater than 75%, greater than 85%, greater than 90%, or greater than 95% of light at that wavelength λ. Adiffuser 22 may optionally be housed between each slit 96 and the correspondinglight detector 14a, 15a, 14b, 15 b.

Aliquid sample 97 is introduced into the sample receiving portion 83 through thesample receiving window 89 using, for example, apipette 98 or similar instrument.Liquid sample 97 is transported alongliquid transport path 99 fromfirst end 100 tosecond end 101 ofporous strips 83, 84, 85, 86 by capillary or wicking action of the pores ofporous strips 83, 84, 85, 86. The sample receiving portion 83 of theporous strip 31 is typically made of fibrous cellulose filter material.

The conjugate portion 84 has been pretreated with at least one particulate labeled binding reagent to bind the analyte to be tested, thereby forming a labeled particle-analyte complex (not shown). The particulate label binding reagent is typically, for example, nano-or micro-sized label particles 32 that have been sensitized to specifically bind to the target analyte. Particles 32 provide a detectable response, which is typically a visible optical response, such as a particular color, but may be in other forms. For example, particles that are visible in the infrared, fluorescent in the ultraviolet, or magnetic may be used. Typically, the engaging portion 84 is treated with a type of particulate labeled binding reagent to test the presence of a type of analyte in theliquid sample 97. However, alternative lateral flow devices may be produced which simultaneously use two or more particulate labelled binding reagents to test two or more analytes. The engagement portion 84 is typically made of fiberglass, cellulose, or surface modified polyester material.

As the flow front of the liquid sample moves into the testing portion 85, the labeled particle-analyte complex and unbound labeled particles are carried toward thesecond end 101. Test portion 85 includes atest area 29 and acontrol area 30, which are monitored by a correspondinglight emitter 13a, 13b in combination with a pair oflight detectors 14a, 15a, 14b, 15 b. Thetest area 29 is pre-treated with an immobilized binding reagent that specifically binds to the label particle-analyte complex and not to unreacted label particles. As the labeled particle-analyte complex is bound in thetest zone 29, the concentration of labeled particles 32 in thetest zone 29 increases. This concentration increase may be monitored by measuring the absorbance oftest area 29 using a correspondinglight emitter 13a, 13b in combination with a pair oflight detectors 14a, 15a, 14b, 15 b. Once the set duration of time has elapsed since the addition of theliquid sample 97, the absorbance of thetest area 29 can be measured. Alternatively, the absorbance of thetest area 29 may be measured continuously or at regular intervals as the lateral flow strips 23 develop.

In order to distinguish between a negative test and a test that does not work properly at all, acontrol zone 30 is typically provided between thetest zone 29 and thesecond end 101. Thecontrol zone 30 is pre-treated with a second immobilized binding reagent that specifically binds to unbound labeled particles and does not bind to the labeled particle-analyte complex. Thus, if the lateralflow test device 82 has operated properly and theliquid sample 97 has passed through the engaging portion 84 and the testing portion 85, thecontrol zone 30 will exhibit a change in absorbance. The absorbance of thecontrol area 30 may be measured by thesecond light emitter 13b in combination with the second pair oflight detectors 14b, 15 b. The test portion 85 is typically made of fibrous nitrocellulose, polyvinylidene fluoride, Polyethersulfone (PES), or a charge modified nylon material. All these materials are fibrous and therefore the sensitivity of the absorbance measurement can be improved by obtaining acorrection signal 21 as described above.

Wickingportion 86, which is provided adjacentsecond end 101, absorbsliquid sample 97 that has passed through testing portion 85 and helps maintainliquid sample 97 in flow communication. The wickingportion 86 is typically made of fibrous cellulose filter material.

Further advantages of the receiver-side differential analysis test device described in this specification with respect to the transmission-sideanalysis test device 1 can be explained with reference to thelateral flow device 82 with integrated analysis test device.

Fig. 23 shows the emission side differentialanalytical test device 1 when thetest zone 29 of the lateralflow test strip 23 is received within thesample receiving portion 7.

The array of alternating first andsecond emitters 2, 3 emitslight 4, 5 towards thesample receiving portion 7. The first andsecond emitters 2, 3 are in the form of OLED devices deposited onto atransparent substrate 102. Said light 4, 5 is detected on the other side of thesample receiving portion 7 by alight detector 8 in the form of a bottom absorbing OPD deposited on the secondtransparent substrate 103.

In practice, it may be difficult to achieve first andsecond emitters 2, 3 whose emission spectra do not overlap and which are arranged to alternate over a sufficiently small distance to provide substantially uniform illumination of thesample receiving portion 7 in each wavelength range. To overcome this problem, an array of white, multi-colored or broadbandlight emitters 128 may be used in conjunction with the array of first andsecond filters 53, 54. However, when using filters 53, 54, the thickness t of thesubstrate 102 means that there will be some crosstalk, since the white, polychromatic or broadbandlight emitters 128 emit white, polychromatic orbroadband light 129 at a range of angles.

This crosstalk can be reduced by reducing the thickness of thesubstrate 102 so that a small portion of white, polychromatic or broadband light 129 from theemitter 128 below thefirst filter 53 is incident on the adjacentsecond filter 54, and vice versa. However, sufficiently thin glass substrates may be difficult to produce and relatively expensive, and it may also be difficult to process and deposit thelight emitters 2, 3 thereon. Thus, in practice, the first andsecond emitters 2, 3 are deposited onto athin substrate 102 made of a polymer material.

Referring also to fig. 24A to 24D, the stability of OLEDs deposited on glass andplastic substrates 102 is compared.

For OLEDs on asubstrate 102 formed of glass, it can be observed that theOLED voltages 104a, 104b and theillumination outputs 105a, 105b measured by OPDs are significantly more stable than thesimilar properties 106a, 106b, 107a, 107b of OLEDs deposited on asubstrate 102 formed of plastic. The data shown in fig. 24A to 24D with dashedlines 104A, 105a, 106a, 107a corresponds to a first test run of about 36s duration, and the data shown withsolid lines 104b, 105b, 106b, 107b corresponds to a second test run of about 6.5s duration. The relatively poor stability of OLEDs deposited on plastic compared to OLEDs deposited on glass may lead to undesirable noise in emission-side differentialanalysis test devices 1. These problems are of particular concern for the emission-side differentialanalysis test device 1, since there may be differences between the measurements obtained at different times, so when there is a difference, the fluctuation in the OLED output will be recorded as a true signal.

In contrast, when filtering on the receiving side, for example using the secondanalytical test device 52, the OLED providing thelight emitter 13 can be deposited on a glass substrate to obtain the benefit of excellent OLED stability. Although the thickness of thesubstrate 37 is still important for reducing cross-talk when the photo-detectors 14,15 arebottom absorbing OPDs 35, it is not expected that OPD stability will be affected in the same way as OLEDs when deposited on plastic, especially because OPDs are not driven by relatively high currents.

Similarly, when thephotodetectors 14,15 are top absorbingOPDs 36 and thefilters 53, 54 are disposed over the encapsulatinglayer 51, the thickness of theencapsulating layer 51 is important to reduce crosstalk. However, cross-talk may also be reduced by placing thefilters 53, 54 under theencapsulation layer 51 or by incorporating thefilters 53, 54 into theencapsulation layer 51.

Method for determining weight coefficients

In equations (1) through (4), weighting coefficients α, β and/or γ are used, these coefficients representing relative weights that account for the absolute sensitivity differences of the first and secondlight detectors 14, 15. the differences are caused by the different materials of the first and secondlight detectors 14,15 and/or the geometry of theanalytical test device 12, 52 as a whole.

The weighting coefficients may be determined by modulating the optical emission of the optical transmitter 13 (e.g., by modulating the input voltage signal) according to a known time-varying signal. The weight coefficients may then be iteratively modified in order to minimize or eliminate the introduced time-varying signal from thecorrection signal 21.

Referring also to fig. 25, an example of determining the weight coefficients α is shown.

An example will be described in the case of a pair of first and secondlight detectors 14,15, such that equation (2) can be expressed as:

I_C＝I₁-αI₂(6)

wherein, I₁Is thesignal 19, I from the first photodetector₂Is thesignal 20, I from thesecond photodetector 15_CTo correct thesignal 21 and α are weighting coefficients.

The time-varyingillumination intensity 108 is produced by modulating the emission of thelight emitter 13 with a square wave signal.

Using a weighting factor α₁To calculate a corresponding correction signal I_C(α₁) Unless the initial guess α₁Perfection, otherwise corresponding correction signal I_C(α₁) Will include components corresponding to the square wave modulation of the illumination intensity a new weighting factor α is determined₂And used to calculate a corresponding correction signal I_C(α₂) The iteration of the value of the weight coefficient α may be performed according to any suitable retrieval strategy the iteration of the weight coefficient α₂、…、α_m-1、α_mUntil the signal I is corrected_C(α_m) Until the component corresponding to the square wave modulation of the illumination intensity is eliminated or reduced below a threshold value, a final convergence weight coefficient α may then be used_mTo calculate thecorrection signal 21 for other devices having the same configuration.

Improvements in or relating to

It will be appreciated that many modifications may be made to the above embodiments. Such modifications may involve equivalent and other features which are already known in the design, manufacture and use of analytical test devices and which may be used instead of or in addition to features already described herein. Features from one embodiment may be substituted for or supplemented by features from another embodiment.

Examples have been described for determining the absorbance of sample 9 in either a transmission or reflection geometry. However, the examples described herein are not limited to absorbance measurements. For example, thelight emitter 13 may emit in a first wavelength range Δ λ_aLight of the first wavelength range DeltaLambda_aExcitation of fluorescence by target analytes or marker particles, and nitrocellulose fibres, e.g. of porous strip 31Background autofluorescence. In contrast to absorbance measurements, the first wavelength range Δ λ is used for fluorescence measurements_aIdeally not in the second or third wavelength range Δ λ_b、Δλ_cOverlap or overlap to a minimum extent. The first and secondlight detectors 14,15 may be for respective second and third wavelength ranges Δ λ_b、Δλ_cSensitive, either inherently or using filters, is chosen such that thefirst light detector 14 measures fluorescence and the secondlight detector 15 measures autofluorescence. Fluorescence wavelength range DeltaLambda_bAnd the autofluorescence wavelength range DeltaLambda_cThere may be some overlap between. The advantage of being able to monitor the first and secondlight detectors 14,15 simultaneously is equally applicable to fluorescence measurements.

Although the embodiments are described with respect to lateralflow test strips 23, the methods of the present invention and first, second and thirdanalytical test devices 12, 52 can also be used with other types of samples 9 with minimal modification.

For example, referring also to fig. 26, a fourthanalytical test device 109 is shown.

The fourthanalytical test device 109 comprises a light path having asample receiving portion 7 adapted to receive a sample 9 in the form of a receptacle, such as acuvette 110, containing aliquid sample 97. Can be in a second wavelength range Delta lambda_bMeasure the absorbance of theliquid sample 97. By obtaining thecorrection signal 21 as the difference between thesignal 19 measured by the one or more first photo-detectors 14 and thesignal 20 measured by the one or more second photo-detectors 15 in the same manner as described above, the detection limit of the fourthanalytical test device 109 can be improved. Similarly, the fourthanalytical test device 109 may be used for fluorescence assays, as described above.

The fourthanalytical test device 109 differs in that, instead of being scattered by thefibers 33, the calibration eliminates the effect of dust, scratches, smudges, etc. on the side of thecuvette 110. In addition, fourthanalytical test device 109 can correct for variations in the amount of suspended particulate matter 111 (FIG. 29) inliquid sample 97. For example, a sample may be obtained from a body of water to check for the concentration of dissolved contaminants. Liquids collected atdifferent timesSample 97 may include varying amounts of silt or other suspended particles. While the sample can be left to settle out the suspended particulate matter 111 (fig. 29), this is impractical for field testing. Selectable second wavelength lambda₂And an associated third wavelength range Δ λ_cSo that the response to the contaminant is of little or no influence and the response to the suspended particulate matter is of a first wavelength lambda₁And a corresponding second wavelength range delta lambda_bSimilarly. In this way, the methods described above can be used to accelerate the process of analyzing aliquid sample 97, whichliquid sample 97 exhibits inherent variability due to, for example, suspended particulate matter 97 (fig. 29).

Referring also to FIG. 27, a fifthanalytical test device 112 is shown.

The fifthanalytical test device 112 comprises an optical path having asample receiving portion 7 adapted to receive a sample in the form of atest plate 113. Theinspection board 113 includes atransparent base 114. A plurality ofhollow cylinders 115 extend perpendicularly from thetransparent base 114 to provide a plurality of sample wells 116, such as a first sample well 116a, asecond sample well 116b, and so forth. Each sample cell 116 may be provided with a differentliquid sample 97. For example, afirst sample well 116a can contain a firstliquid sample 97a, asecond sample well 116b can contain a secondliquid sample 97b, and so on. The sample trench 116 may extend in one direction. More typically, the sample wells 116 extend in two directions to form an array. Theinspection plate 113 may be moved so that each sample well 116 is in turn located in thesample receiving portion 7 of the optical path. To determine the concentration of an analyte or marker in theliquid sample 97, the above-described method can be performed with respect to absorbance (transmittance) or fluorescence measurements.

Alternatively, thelight emitter 13 andlight detectors 14,15 may be movable relative to theinspection board 112. The fifthanalytical test device 112 may comprise a plurality of pairs oflight emitters 13 and correspondinglight detectors 14, 15. This can allow for the simultaneous measurement of an entire row/column of the array of sample wells 116, or even anentire test plate 113.

When sample 9 was a plaque, the source of the non-uniformity was notfiber 33. Similar to thecuvette 110, dust, scratches, smudges, etc. on theinspection plate 113 may cause undesirable effectsThe scattering of the view. In addition, theinterface 117 between theliquid sample 97 and the air (also sometimes referred to as the meniscus 117) also affects the amount of light received at thephotodetectors 14, 15. This can be particularly significant when the diameter of the sample cell 116 is small. Contamination or imperfections on the inner surface of thecylinder 115 can cause the meniscus to deviate from the ideal shape, resulting in non-uniformity in transmitted light between different sample wells 116. Even in the absence of contaminants or defects on the inner surface ofcylinder 115,different liquid samples 97 may have different surface tensions, resulting in a change in the curvature ofmeniscus 117. Small changes in solute content can have a disproportionate effect on surface tension. Although in the second and third wavelength ranges Δ λ_b、Δλ_cThe scattering of light through themeniscus 117 will have a slight wavelength dependence, but the corrective methods described above can reduce the effects of non-uniformity among different test slots 116. The calibration method can be used whether the sample well 116 is illuminated from above or below.

Referring also to fig. 28, a sixthanalytical test device 118 is shown.

The sixthanalytical test device 118 includes an optical path having asample receiving portion 7 extending perpendicular to thechannel 119. Thechannel 119 is defined bywalls 120 and includes awindow 121 to allow light 17, 18 from thelight emitter 13 to pass through thechannel 119. Alternatively, if thewall 120 is transparent, thewindow 121 may not be needed. Thechannel 119 may be a pipe. The liquid flows through thechannel 119 in aflow direction 122. The liquid may comprise suspendedparticulate matter 111, such as silt in river water.

The sixthanalytical test device 118 may be used to analyze the concentration of contaminants or other analytes present in a liquid flowing through the channel. Generally, the amount ofparticulate matter 111 suspended in the liquid flowing through thechannel 119 may vary over time. Non-uniformities in background absorption/scattering due to suspendedparticulate matter 111 can adversely affect both the detection limit and the resolution of detecting monitored contaminants or other analytes. Selectable second wavelength lambda₂And a corresponding third wavelength range Δ λ_cSo as to respond little or no to contaminants and to suspended particlesResponse of particulate matter and first wavelength lambda₁And a corresponding second wavelength range delta lambda_bSimilarly. In this way, the methods described above can be used to accelerate the process of analyzing flowing liquids that exhibit inherent variability due to, for example, suspended particulate matter. The use of first andsecond photodetectors 14,15 is particularly advantageous when the flow rate through thechannel 119 is high, as compared to alternating illumination of the first andsecond emitters 2, 3.

Referring also to FIG. 29, a seventhanalytical test device 123 is shown.

The seventhanalytical test device 123 comprises a light path having asample receiving portion 7 adapted to receive amicrofluidic channel 124 perpendicular to the light path. Themicrofluidic channel 124 is defined bywalls 125 and contains a carrier medium (e.g., oil) that flows through themicrofluidic channel 124 in aflow direction 126. Thedroplet 127 of the second liquid (typically water) contains the analyte or label, using a wavelength range Δ λ_bThe corresponding light 17 measures the concentration of the analyte or marker within thedroplet 127. Themicrofluidic channel 124 may be in the form of a length of tubing or a channel machined into a polymeric material. Using a third wavelength range Δ λ_cMeasurements taken of the correspondinglight 18 can be used to compensate for scattering or absorption caused by imperfections or contamination of thewalls 125 of themicrofluidic channel 124.

In any of the fourth, fifth, sixth and seventhanalytical test devices 109, 112, 118, 123, the first andsecond photodetectors 14,15 may be configured to couple the respective second and third wavelength ranges Δ λ through one of_b、Δλ_cAnd (3) sensitivity:

inherently different wavelength sensitivity, as in the firstanalytical test device 12;

first andsecond filters 53, 54, as in the secondanalytical test device 52; or

Using a modified top absorbing OPD66 withmicrocavity 75 and with a tunable resonant wavelength, as in a third analytical test setup.

Although the advantages of using OLEDs deposited on a glass substrate have been described above, the invention can also be implemented usinglight emitters 13 in the form of OLEDs deposited on a plastic substrate.

Although claims have been formulated in this application to particular combinations of features, it should be understood that the scope of the disclosure of the present invention also includes any novel feature or any novel combination of features disclosed herein either explicitly or implicitly or any generalisation thereof, whether or not it relates to the same invention as presently claimed in any claim and whether or not it mitigates any or all of the same technical problems as does the present invention. The applicants hereby give notice that new claims may be formulated to such features and/or combinations of such features during the prosecution of the present application or of any further application derived therefrom.

Claims (30)

1. An analytical test device comprising:

one or more light emitters configured to emit light in a first wavelength range;

one or more first light detectors, each first light detector being sensitive to a second range of wavelengths around the first wavelength;

one or more second light detectors, each second light detector being sensitive to a third range of wavelengths around a second wavelength, the second wavelength being different from the first wavelength;

a correction module configured to receive signals from the first photodetector and the second photodetector and to generate a correction signal based on a difference in weight of the signals from the first photodetector and the second photodetector;

wherein the test device is configured such that light from the light emitter reaches the first light detector and the second light detector via an optical path that includes the sample receiving portion.

2. The analytical test device of claim 1, wherein the plurality of first light detectors and the plurality of second light detectors are arranged in an alternating manner.

3. An analytical test device according to claim 1 or claim 2, wherein a part of each first light detector or each first light detector extends in the first direction and a part of each second light detector or each second light detector extends in the first direction.

Wherein the first light detector and the second light detector or parts thereof are interleaved in a second direction substantially perpendicular to the first direction.

4. The analytical test device according to claim 1 or claim 2, wherein a plurality of first light detectors are arranged in a first lattice and a plurality of second light detectors are arranged in a second lattice, wherein the first and second lattices are arranged to intersect.

5. The analytical test device of any preceding claim, wherein the light path further comprises a light diffuser disposed between the sample receiving portion and the light detector.

6. The analytical test device according to any one of claims 1 to 5, wherein the optical path is configured such that the first and second light detectors receive light transmitted through the sample receiving portion.

7. The analytical test device according to any one of claims 1 to 5, wherein the optical path is configured such that the first and second light detectors receive light reflected from the sample receiving portion.

8. The analytical test device according to any one of claims 1 to 7, wherein each first light detector comprises a first light sensitive material sensitive to a second wavelength range, and wherein each second light detector comprises a second light sensitive material sensitive to a third wavelength range.

9. The analytical test device of any one of claims 1 to 7, wherein:

each first light detector comprises a light sensitive material and a first filter, wherein the first filter is arranged to filter light arriving via the optical path, to transmit the second wavelength range, and to attenuate the third wavelength range; and

each second light detector comprises a light sensitive material and a second filter, wherein the second filter is arranged to filter light arriving via the light path, to transmit a third wavelength range and to attenuate the second wavelength range.

10. The analytical test device of any one of claims 1 to 7, wherein each first light detector includes a light sensitive material and each second light detector includes a light sensitive material, further comprising:

a first filter corresponding to each first light detector, wherein the first filter is arranged to filter light arriving via the optical path, to transmit the second wavelength range, and to attenuate the third wavelength range; and

a second filter corresponding to each second light detector, wherein the second filter is arranged to filter light arriving via the optical path, to transmit the third wavelength range, and to attenuate the second wavelength range.

11. The analytical test device of any one of claims 1 to 7, wherein:

each first photodetector includes a photosensitive material and a first resonant cavity configured to have a resonant wavelength within a second wavelength range;

each second photodetector includes a photosensitive material and a second resonant cavity configured to have a resonant wavelength within a third wavelength range.

12. The analytical test device of any preceding claim, wherein each light emitter comprises an organic light emitting diode.

13. The analytical test device of claim 12, wherein the organic light emitting diodes are disposed on one or more glass substrates.

14. The analytical test device of any preceding claim, wherein the first and second photodetectors are organic photodetectors.

15. The analytical test device of claim 14, wherein the first and second photodetectors are top absorption organic photodetectors.

16. The analytical test device of claim 14, wherein the first and second photodetectors are bottom absorption organic photodetectors.

17. The analytical test device according to any preceding claim, wherein the correction signal is generated according to the following equation:

wherein I_CTo correct the signal, I¹_nIs the signal from the nth one of the N first photodiodes, I²_nFor the signal from the nth of the N second photodiodes, α is a predetermined weighting factor, and N is a real positive integer satisfying N ≧ 1.

18. The analytical test device of any preceding claim, wherein the correction module comprises a microprocessor or microcontroller.

19. The analytical test device of any preceding claim, wherein the correction module comprises a summing amplifier circuit configured to generate the correction signal based on inputs received from the first and second light detectors.

20. The analytical test device according to any one of claims 1 to 19, wherein the first wavelength is within the first wavelength range, the second wavelength is within the first wavelength range, and the analytical test device is configured to measure absorbance of a sample.

21. The analytical test device of any one of claims 1 to 19, wherein the first wavelength is outside the first wavelength range, the second wavelength is outside the first wavelength range, and the analytical test device is configured to measure fluorescence of a sample.

22. The analytical test device of any one of claims 1 to 21, wherein the sample receiving portion of the optical path is configured to receive a lateral flow test strip.

23. The analytical test device of any one of claims 1 to 21, wherein the sample receiving portion of the optical path is configured to receive a cuvette.

24. The analytical test device of any one of claims 1 to 21, wherein the sample receiving portion of the optical path is configured to receive a test well plate.

25. The analytical test device of any one of claims 1 to 21, wherein the sample receiving portion of the optical path is configured to receive all, a portion, or a channel of a microfluidic device.

26. The analytical test device of any one of claims 1 to 21, further comprising:

a liquid transport path for transporting a liquid sample received near one end of the liquid transport path through the sample receiving portion of the optical path.

27. A lateral flow testing device comprising:

the analytical test device according to any one of claims 1 to 22; and

a lateral flow test strip arranged such that a test region is disposed within the sample receiving portion.

28. The lateral flow test device of claim 27, wherein the lateral flow test strip includes marker particles, and wherein the marker particles have a greater absorbance of light in the second wavelength range than in the third wavelength range.

29. A method of analysing a sample using an analytical test device according to any one of claims 1 to 26 or a lateral flow test device according to claim 27 or 28, the method comprising:

receiving signals from a first photodetector and a second photodetector;

a corrected signal is generated based on a difference in weight of signals from the first photodetector and the second photodetector.

30. A method of determining one or more weight coefficients for determining a correction signal in an analytical test device according to any one of claims 1 to 26 or a lateral test device according to claim 27 or 28, the method comprising:

modulating the light emission intensity of one or more light emitters according to a known time-varying signal;

one or more of the weight coefficients are iteratively adjusted to minimize or eliminate the time-varying signal in the correction signal.

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